We have established a Consortium Tissue Core to process, store, and distribute samples from patients with Chronic Lymphocytic Leukemia. One of the aims of this proposal is to continue to serve as a repository for all CLL samples from patients diagnosed and collected at the participating CRC clinical sites. The processing, storage, and distribution of each sample will be performed according to established standard operating procedures in accordance with HIPAA regulations. The Tissue Core will also perform a basic set of assays on all viably stored CLL samples from each patient upon initial receipt. These tests will include: immunophenotyping to determine the surface antigen phenotype, ZAP-70 expression, and determination of the expressed immunoglobulin heavy chain gene (IgVH) mutational status. Testing for Minimal Residual Disease (MRD), soluble CD20/CD52 (rituximab/alemtuzumab), and B CLL turnover rates will be performed on specific CLL samples enrolled in clinical trials during follow-up and pre &post therapy as needed. In addition, the serial samples of specific CLL patients will be characterized according to their surface antigen phenotype by multiparameter flow cytometric analysis. This will allow the CRC investigators to examine for longitudinal changes in the leukemia cell's genotype, biochemistry, and/or immunologic phenotype and correlate these data to clinical outcome. The Tissue Core will seek to standardize interphase Fluorescence in situ Hybridization (FISH) studies by distributing specific characterized CLL samples to the participating CRC cytogenetics sites at which FISH analysis will be conducted. This validation will provide innovative and accurate interphase FISH studies for CRC clinical trials and research investigators. The Tissue Core will also collect, process, and validate specimens from affected family members with CLL for targeted genetic studies performed by CRC investigators. Finally, the Tissue Core will distribute specific characterized samples as requested by CRC investigators for hypothesis driven studies. This trafficking of characterized CLL samples, with their associated clinical and demographic data, will enable and facilitate the development of new CLL therapies.